Hsa_circ_0058092 Protects Against Hyperglycemia-Induced Endothelial Progenitor Cell Damage Via Mir-217/Foxo3

Circular RNAs (circRNAs) regulate the expression of genes that are critical for various biological and pathological processes. Previous studies have reported that the expression of hsa_circ_0058092 is decreased in patients with diabetes mellitus (DM); however, the specific role of this circRNA in DM is unknown. In the present study, endothelial progenitor cells (EPCs) were isolated and a decreased hsa_circ_0058092 expression was found under conditions of hyperglycemia (HG). The overexpression of hsa_circ_0058092 protected the EPCs against HG-induced damage by preserving cell survival, proliferation, migration and angiogenic differentiation. The overexpression of hsa_circ_0058092 also decreased the HG-induced increase in NADPH-oxidase proteins and inflammatory cytokines. Further investigation revealed that the overexpression of hsa_circ_0058092 enhanced FOXO3 expression, which was mediated through the interaction with miR-217. Furthermore, the upregulation of miR-217 or the downregulation of FOXO3 abolished the protective effects of hsa_circ_0058092 against HG-induced EPC damage. On the whole, these data suggest that hsa_circ_0058092 acts via the miR-217/FOXO3 pathway to protect against EPCs HG-induced damage, and to preserve the migration and angiogenesis of EPCs.